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Research ArticleArticle

Metabolism and Disposition Kinetics of Nicotine

Janne Hukkanen, Pleyton Jacob III and Neal L. Benowitz
Pharmacological Reviews March 2005, 57 (1) 79-115; DOI: https://doi.org/10.1124/pr.57.1.3
Janne Hukkanen
Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, and the Departments of Medicine and Psychiatry, University of California, San Francisco, California
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Pleyton Jacob III
Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, and the Departments of Medicine and Psychiatry, University of California, San Francisco, California
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Neal L. Benowitz
Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, and the Departments of Medicine and Psychiatry, University of California, San Francisco, California
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Abstract

Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current knowledge about the metabolism and disposition kinetics of nicotine, some other naturally occurring tobacco alkaloids, and nicotine analogs that are under development as potential therapeutic agents. The focus is on studies in humans, but animal data are mentioned when relevant to the interpretation of human data. The pathways of nicotine metabolism are described in detail. Absorption, distribution, metabolism, and excretion of nicotine and related compounds are reviewed. Enzymes involved in nicotine metabolism including cytochrome P450 enzymes, aldehyde oxidase, flavin-containing monooxygenase 3, amine N-methyltransferase, and UDP-glucuronosyltransferases are represented, as well as factors affecting metabolism, such as genetic variations in metabolic enzymes, effects of diet, age, gender, pregnancy, liver and kidney diseases, and racial and ethnic differences. Also effects of smoking and various inhibitors and inducers, including oral contraceptives, on nicotine metabolism are discussed. Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme.

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Pharmacological Reviews: 57 (1)
Pharmacological Reviews
Vol. 57, Issue 1
1 Mar 2005
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Research ArticleArticle

Metabolism and Disposition Kinetics of Nicotine

Janne Hukkanen, Pleyton Jacob and Neal L. Benowitz
Pharmacological Reviews March 1, 2005, 57 (1) 79-115; DOI: https://doi.org/10.1124/pr.57.1.3

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Research ArticleArticle

Metabolism and Disposition Kinetics of Nicotine

Janne Hukkanen, Pleyton Jacob and Neal L. Benowitz
Pharmacological Reviews March 1, 2005, 57 (1) 79-115; DOI: https://doi.org/10.1124/pr.57.1.3
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  • Article
    • Abstract
    • I. Introduction
    • II. Nicotine and Related Alkaloids in Tobacco Products
    • III. Absorption of Nicotine from Tobacco Smoke and Nicotine Medications
    • IV. Distribution of Nicotine in Body Tissues
    • V. Nicotine and Cotinine Blood Levels during Tobacco Use and Nicotine Replacement Therapy
    • VI. Metabolism of Nicotine
    • VII. Excretion
    • VIII. Species Differences in Nicotine Metabolism
    • IX. Metabolism of Minor Alkaloids of Tobacco
    • X. Pharmacokinetics and Metabolism of Nicotine Analogs
    • XI. Conclusions and Areas for Further Study
    • Acknowledgments
    • Footnotes
    • References
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